The epidemiology of fungal infections is an evolving issue since the late 1960s when, as a consequence of the development of antibiotic therapies, a drastic rise of mycoses was observed. Today, fungal infections represent a major global health threat and the increasing incidence of invasive and opportunistic mycoses is often associated with excessive morbidity and mortality. Fungal infections have increased in incidence during last decades often as a result of advanced medical treatments and of the increasing number of immunocompromised patients.1 
The diagnosis and the treatment of fungal infections are challenging tasks complicated by differences in patient populations and the growing variety of pathogens. Although several species of fungi are potentially pathogenic in humans Candida, and in particular Candida albicans, is the organism responsible for most of fungal diseases.2 
Therapy against Candida infections relies on the use of a limited number of chemotherapeutic agents, including azoles, such as fluconazole and voriconazole, and polyenes, such as amphotericin B. Despite the fact that these molecules constitute the preferred first line therapy, the emergence and the spread of drug resistant fungal species limit their use. Today, fluconazole is poorly or not effective against mutant Candida species3. Therefore there is the need for the development of new and more active molecules, in particular active against multi-resistant species.
Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel antifungals. Chitin is a polymer of N-acetylglucosamine (GlcNAc) with a β-1,4 linkage between monomers. Family 18 of glycosyl hydrolases encompasses chitinases. Chitinases are the enzymes responsible for chitin degradation; they have been validated as a potential target for the design of new therapeutic agents active against fungal infections.6-8 
Mammals are not known to synthesize chitin or to metabolize it as a nutrient, yet the human genome encodes eight well-documented genes for proteins now classified as glycoside hydrolase family18 members. Members of this family are known to adopt the TIM (triosephosphate isomerase) fold consisting of a strongly conserved (β/α)8-barrel structure. Often, separate chitin-binding domains (CBM14) are present in the carboxyl terminal region of the proteins (additional file 1: GH18 family domain structure). The protein family includes chitinases as well as homologous proteins termed chitolectins. The latter lack the key active-site glutamate residue that donates a proton required for hydrolytic enzyme activity, but retain highly conserved residues involved in oligosaccharide binding and overall three-dimensional structure. Traditionally, chitinases are classified in two glycoside hydrolase families, GH18 and GH19, with different structures and catalytic mechanisms. Family GH18 includes the chitinases from viruses, bacteria, fungi and animals as well as classes III and V from plants. The GH19 chitinases are identified mostly in plants (classes I, II and IV), nematodes, and some bacteria. Recent data indicate chitinase activity is also present in protein families GH48 and GH20. N-acetyl-β-D-glucosaminidases such as those in family GH20 also can participate in chitin degradation by hydrolyzing GlcNAc from the non-reducing end of chito-oligosaccharides.
Although chitin itself does not exist in humans, chitinases are present in the human genome. Human chitinase family members includes acidic mammalian chitinase (AMCase). AMCase is relatively abundant in the gastrointestinal tract and is found to a lesser extent in the lung in rodents and man10. Recently, AMCase has been shown to be induced via a Thelper-2-specific, interleukin-13-mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyper-responsiveness. Inhibition of AMCase associated with parasitic infection decreases the recruitment of inflammatory cells and profoundly dampens T helper 2 (Th2) cellular responses in a murine model of lung inflammation, suggesting that this enzyme may be a potential target for an asthma drug therapy.9 It has also been reported that AMCase over expression inhibits growth factor withdrawal and FasL induced epithelial cell apoptosis11. Both the Th2 inflammatory response and a disrupted proliferation/apoptosis cell ratio have been identified as driving mechanisms behind asthma, suggesting that this enzyme will be a promising target for an asthma drug therapy.
WO 2009/113033 relates to cyclic guanidine derivatives used as antifungal agents in particular against Candida species, having the general formula:
